Towards Blood Flow in the Virtual Human: Efficient Self-Coupling of HemeLB

Many scientific and medical researchers are working towards the creation of a virtual human - a personalised digital copy of an individual - that will assist in a patient's diagnosis, treatment and recovery. The complex nature of living systems means that the development of this remains a major challenge. We describe progress in enabling the HemeLB lattice Boltzmann code to simulate 3D macroscopic blood flow on a full human scale. Significant developments in memory management and load balancing allow near linear scaling performance of the code on hundreds of thousands of computer cores. Integral to the construction of a virtual human, we also outline the implementation of a self-coupling strategy for HemeLB. This allows simultaneous simulation of arterial and venous vascular trees based on human-specific geometries.Comment: 30 pages, 10 figures, To be published in Interface Focus (https://royalsocietypublishing.org/journal/rsfs

The XMM Cluster Survey: The Stellar Mass Assembly of Fossil Galaxies

This paper presents both the result of a search for fossil systems (FSs) within the XMM Cluster Survey and the Sloan Digital Sky Survey and the results of a study of the stellar mass assembly and stellar populations of their fossil galaxies. In total, 17 groups and clusters are identified at z < 0.25 with large magnitude gaps between the first and fourth brightest galaxies. All the information necessary to classify these systems as fossils is provided. For both groups and clusters, the total and fractional luminosity of the brightest galaxy is positively correlated with the magnitude gap. The brightest galaxies in FSs (called fossil galaxies) have stellar populations and star formation histories which are similar to normal brightest cluster galaxies (BCGs). However, at fixed group/cluster mass, the stellar masses of the fossil galaxies are larger compared to normal BCGs, a fact that holds true over a wide range of group/cluster masses. Moreover, the fossil galaxies are found to contain a significant fraction of the total optical luminosity of the group/cluster within 0.5R200, as much as 85%, compared to the non-fossils, which can have as little as 10%. Our results suggest that FSs formed early and in the highest density regions of the universe and that fossil galaxies represent the end products of galaxy mergers in groups and clusters. The online FS catalog can be found at http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.html.Comment: 30 pages, 50 figures. ApJ published version, online FS catalog added: http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.htm

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.&lt;p&gt;&lt;/p&gt; Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).&lt;p&gt;&lt;/p&gt; Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.&lt;p&gt;&lt;/p&gt; Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’

The Expanding Fireball of Nova Delphini 2013

A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting from one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 +/- 0.59 kpc from the Sun.Comment: Published in Nature. 32 pages. Final version available at http://www.nature.com/nature/journal/v515/n7526/full/nature13834.htm

Treatment costs and priority setting in health care: A qualitative study

The aim of this study is to investigate whether the public believes high cost patients should be a lower priority for public health care than low cost patients, other things being equal, in order to maximise health gains from the health budget. Semi-structured group discussions were used to help participants reflect critically upon their own views and gain exposure to alternative views, and in this way elicit underlying values rather than unreflective preferences. Participants were given two main tasks: first, to select from among three general principles for setting health care priorities the one that comes closest to their own views; second, to allocate a limited hospital budget between two groups of imaginary patients. Forty-one people, varying in age, occupation, income and education level, participated in a total of six group discussions with each group comprising between six and eight people

Modern optical astronomy: technology and impact of interferometry

The present `state of the art' and the path to future progress in high spatial resolution imaging interferometry is reviewed. The review begins with a treatment of the fundamentals of stellar optical interferometry, the origin, properties, optical effects of turbulence in the Earth's atmosphere, the passive methods that are applied on a single telescope to overcome atmospheric image degradation such as speckle interferometry, and various other techniques. These topics include differential speckle interferometry, speckle spectroscopy and polarimetry, phase diversity, wavefront shearing interferometry, phase-closure methods, dark speckle imaging, as well as the limitations imposed by the detectors on the performance of speckle imaging. A brief account is given of the technological innovation of adaptive-optics (AO) to compensate such atmospheric effects on the image in real time. A major advancement involves the transition from single-aperture to the dilute-aperture interferometry using multiple telescopes. Therefore, the review deals with recent developments involving ground-based, and space-based optical arrays. Emphasis is placed on the problems specific to delay-lines, beam recombination, polarization, dispersion, fringe-tracking, bootstrapping, coherencing and cophasing, and recovery of the visibility functions. The role of AO in enhancing visibilities is also discussed. The applications of interferometry, such as imaging, astrometry, and nulling are described. The mathematical intricacies of the various `post-detection' image-processing techniques are examined critically. The review concludes with a discussion of the astrophysical importance and the perspectives of interferometry.Comment: 65 pages LaTeX file including 23 figures. Reviews of Modern Physics, 2002, to appear in April issu

Gas exchange at whole plant level shows that a less conservative water use is linked to a higher performance in three ecologically distinct pine species

Increasing temperatures and decreasing precipitation in large areas of the planet as a consequence of global warming will affect plant growth and survival. However, the impact of climatic conditions will differ across species depending on their stomatal response to increasing aridity, as this will ultimately affect the balance between carbon assimilation and water loss. In this study, we monitored gas exchange, growth and survival in saplings of three widely distributed European pine species (Pinus halepensis, P. nigra and P. sylvestris) with contrasting distribution and ecological requirements in order to ascertain the relationship between stomatal control and plant performance. The experiment was conducted in a common garden environment resembling rainfall and temperature conditions that two of the three species are expected to encounter in the near future. In addition, gas exchange was monitored both at the leaf and at the whole-plant level using a transient-state closed chamber, which allowed us to model the response of the whole plant to increased air evaporative demand (AED). P. sylvestris was the species with lowest survival and performance. By contrast, P. halepensis showed no mortality, much higher growth (two orders of magnitude), carbon assimilation (ca. 14 fold higher) and stomatal conductance and water transpiration (ca. 4 fold higher) than the other two species. As a consequence, P. halepensis exhibited higher values of water-use efficiency than the rest of the species even at the highest values of AED. Overall, the results strongly support that the weaker stomatal control of P. halepensis, which is linked to lower stem water potential, enabled this species to maximize carbon uptake under drought stress and ultimately outperform the more water conservative P. nigra and P. sylvestris. These results suggest that under a hotter drought scenario P. nigra and P. sylvestris would very likely suffer increased mortality, whereas P. halepensis could maintain gas exchange and avoid water-induced growth limitation. This might ultimately foster an expansion of P. halepensis to higher latitudes and elevations.This work was supported by the projects ECOLPIN (AGL2011–24296) and Remedinal 3 (S2013/ MAE- 2719) of the Madrid Government, by a FPU fellowship from the Spanish Ministry of Education, Culture and Sport (FPU13/03410) to DS and by EU Marie Curie (FP7–2013-IOF-625988) fellowship to EPSC

Integrating an internet-mediated walking program into family medicine clinical practice: a pilot feasibility study

<p>Abstract</p> <p>Background</p> <p>Regular participation in physical activity can prevent many chronic health conditions. Computerized self-management programs are effective clinical tools to support patient participation in physical activity. This pilot study sought to develop and evaluate an online interface for primary care providers to refer patients to an Internet-mediated walking program called Stepping Up to Health (SUH) and to monitor participant progress in the program.</p> <p>Methods</p> <p>In Phase I of the study, we recruited six pairs of physicians and medical assistants from two family practice clinics to assist with the design of a clinical interface. During Phase II, providers used the developed interface to refer patients to a six-week pilot intervention. Provider perspectives were assessed regarding the feasibility of integrating the program into routine care. Assessment tools included quantitative and qualitative data gathered from semi-structured interviews, surveys, and online usage logs.</p> <p>Results</p> <p>In Phase I, 13 providers used SUH and participated in two interviews. Providers emphasized the need for alerts flagging patients who were not doing well and the ability to review participant progress. Additionally, providers asked for summary views of data across all enrolled clinic patients as well as advertising materials for intervention recruitment. In response to this input, an interface was developed containing three pages: 1) a recruitment page, 2) a summary page, and 3) a detailed patient page. In Phase II, providers used the interface to refer 139 patients to SUH and 37 (27%) enrolled in the intervention. Providers rarely used the interface to monitor enrolled patients. Barriers to regular use of the intervention included lack of integration with the medical record system, competing priorities, patient disinterest, and physician unease with exercise referrals. Intention-to-treat analyses showed that patients increased walking by an average of 1493 steps/day from pre- to post-intervention (<it>t </it>= (36) = 4.13, <it>p </it>< 0.01).</p> <p>Conclusions</p> <p>Providers successfully referred patients using the SUH provider interface, but were less willing to monitor patient compliance in the program. Patients who completed the program significantly increased their step counts. Future research is needed to test the effectiveness of integrating SUH with clinical information systems over a longer evaluation period.</p

Probabilistic (logic) programming concepts

A multitude of different probabilistic programming languages exists today, all extending a traditional programming language with primitives to support modeling of complex, structured probability distributions. Each of these languages employs its own probabilistic primitives, and comes with a particular syntax, semantics and inference procedure. This makes it hard to understand the underlying programming concepts and appreciate the differences between the different languages. To obtain a better understanding of probabilistic programming, we identify a number of core programming concepts underlying the primitives used by various probabilistic languages, discuss the execution mechanisms that they require and use these to position and survey state-of-the-art probabilistic languages and their implementation. While doing so, we focus on probabilistic extensions of logic programming languages such as Prolog, which have been considered for over 20 years